Preparation of 2-keto aldonic acids from aldonic acids by anodic oxidation



15 tion as 35 obtained Patented Nov. 19, 1940 UNITED STATES PATENT OFFICE PREPARATION OF 2-KETO ALDONIC ACIDS FROM ALDONIC ACIDS BY ANODIC OXI- DATION No Drawing. Application December 15, 1938, Serial No. 245,906

6 Claims.

This invention relates to the preparation of 2-keto aldonic acids from aldonic acids by anodic oxidation and has for its object to provide a new and improved process for this purpose.

Many attempts have been made to prepare 2-keto-ald0nic acids by the chemical oxidation of the corresponding aldonic acids or sugars. Such a process is disclosed by our copending U. S. application S. N. 227,964, filed September 1, 1938. However, no principles are known by which the nature of the oxidation produced by a particular agent can be predicted.

It has also been attempted 'to oxidize sugars electrolytically, for instance with bromide soluthe electrolyte. The aldoses have been oxidized to the corresponding aldonic acids (U. S. Pat. No. 1,937,273 of November 28, 1933, and No. 1,976,731 of October 16, 1934). In these processes there is no indication that the aldonic 20 acids can be further oxidized. According to Neuberg (Biochem. Z. 72527-8) and Neuberg, Scott and Lachmann (Biochem. Z. 241152-65) metallic salts of aldonic acids such as copper salts of aldonic acids have been converted by 25 meansof the electric current to 'the next lower carbon sugars.

Neuberg suggests in his preliminary paper (Biochem. Z. 7:527-8) that Z-keto acids would probably result as a by-product from the con- 30 ditions of his electrolytic experiments. However,

he never established that such is the case. The experimental results of Neuberg and his collaborators published in the subsequent paper (Biochem. Z. 241152-455) definitely show that they only the lower carbon sugars. 'We have repeated Neubergs experiments and confirm his results and observations.

However, we have found that an electrolytic process involving the combined action of a halide,

other than an iodide, and soluble chromium compounds will convert the aldonic acids to the corresponding Z-lreto-acids. The following acids have been subjected to the oxidation and found to give substantial quantities of reducing acid:

45 Gluconic, mannonic, idonic, gulonic, galactonicand arabonic. The most favorable conditions are obtained by using a salt of an aldonic acid, preferably alkali or alkaline earth metal salts in the presence of a soluble halide, other than an iodide,

m and chromic acid in a weakly acid solution.

Acetic acid is a suitable acidifying agent. Graphite electrodes are eflicient for this purpose and there is no advantage in the use of a diaphragm. The current density is not critical. The amount 55 of chromic acid required is only about of that theoretically necessary for a complete oxidation, and the process may be successfully operated with as little as 3 of the theoretical amount of chromic acid. It is not necessary to have the chromium present in the form of chromic acid at the beginning of the electrolysis, it may be present in a lower valency.

The progress of the oxidation can be followed by repeated determinations of the reducing power of the reaction mixture by means of Fehlings solution. By continuing the electrolysis to the maximum reduction of Fehlings solution yields up to 80% are obtainable, using as a basis of calculation the reducing power of the particular keto acid.

The relatively small smount of chromium required in this process is of great advantage in the isolating of the keto acids because there is correspondingly less formation of complex chromium compounds which are subject to direct removal only in the form of ferri or term cyanide complexes. In fact, a substantial quantity of the keto acids can be separated without previous removal of the chromium.

EXAMPLE 1 Electra-oxidation of sodium-1 -idona.te to sodium- 2-lceto-1 -idonate 109 grams of sodium idonate, 50 grams of sodium bromide, 60 cc. of glacial acetic acid and 5 grams of chromium trioxide are dissolved in water and diluted to one liter. The mixture is transferred to an electrolyticcell containing two graphite electrodes and a stirrer. The subsequent electrolytic oxidation is'carried out a current density of about 4 arnp./dm. (area of electrode 1.3 dmfi) and at a temperature of about 20 C. After four hours a Fehlings reduction indicates that more than a 50% yield, calculated as sodium-z-keto-idonate.

We prefer to interrupt the electrolytic oxidation at this point and recover unchanged idonate to avoid undue decomposition. The electrolyte is evaporated under diminished pressure until it weighs about 350 grams. The concentrated solulution is warmed and slowly treated with 350 cc. of methyl alcohol, whereupon the sodium-Z-ketoidonate crystallizes immediately.

The crystalline salt is filtered and washed with 70% methyl alcohol until free oi chromium ions. The white crystalline salt is sodium-2-keto-1- idonate-monohydrate, identical with sodium-2'- keto-l-gulonate. Its physical constants correspond to those of the compound reported by Micheel, Kraft and Lehman (Z. physiol, Chem.

Its melting .point is 145 C., rotation at 20 C. is 23.6

225:13-27, 1934). and its specific The free 2-keto idonic acid was identified by decomposing 30 grams 01' the sodium-2-ketoidonate with dilute sulfuric acid containing 6.3 grams H2804. The sodium sulphate was precipitated by an addition of ethyl alcohol, filtered and the filtrate evaporated to about 30 cc.; whereupon the free acid crystallized. It was then recovered by filtering and washing with 80% acetone. This acid analyzed 100.1% as the monohydrate. A sample of the monohydrate was dehydrated in a vacuum dryer and showed a melting point of 171 C. This is identical with the anhydrous 2-keto-gulonic acid reported by Reichstein and Gruessner (Helv. Chim. Acta 17:,311-328, 1934).

ExArrPLn 2 Electra-oxidation of calcium d-gluconate to calcz'um Z-Iceto-d-gluconate 112 grams of calcium gluconate monohydrate, 100 grams of calcium bromide, 60 cc. of glacial acetic acid and 5 grams of chromium trioxide are dissolved in water and diluted to one liter. The electrolytic oxidation is performed under the same conditions as described in Example 1. After electrolyzing for about 6 hours a Fehlings reduction indicates an 80% yield as calcium 2- keto-gluconate.

Since calcium bromide forms addition compounds with calcium gluconate and calcium 2- keto-gluconate, the separation in this particular example is efiected by converting the latter into insoluble basic calcium salts, while the calcium bromide remains dissolved.

To accomplish this the electrolyte is cooled to about 5 and then treated with a slurry of hydrated lime (150 grams) and about of a volume of ethyl alcohol. The precipitated calcium salts are filtered, washed and the organic acids are liberated by the addition of dilute sulfuric acid, whereupon the calcium sulphate is removed by filtration. The bromide-free solution is now treated with sufficient oxalic acid to completely remove the calcium and the calcium oxalate is filtered. The filtrate is treated with 6.5 grams hydroferrocyanic acid to react with the chromium and the solution is evaporated to dryness. The residue is then taken up with methyl alcohol, refiuxed for a few minutes, and the insoluble chromium ferrocyanide compound removed by filtration.

The methyl alcoholic filtrate is concentrated under diminished pressure to about 200 cc. and a sufilcient quantity of a strong methyl alcoholic. hydrochloric acid is added to make the reaction mixture 1% H01.

After about 24 hours standing the crystallized 2-keto-d-gluconic methyl ester is recovered. It has a melting point of 174-176 C., and its specific rotation at equilibrium[a]n=76.8 (C=2.8 grams/100 cc. (Ohle, Ber. 63:849, 1930) A portion of the methyl ester was converted to isoascorbic acid by the method 01 Maurer and Schiedt (Berichte 67Bzl239-4l, 1934). Pure isoascorbic acid was isolated and showed a melting point of 166 C. and a specific rotation An iodine analysis indicates 99% purity calculated as isoascorbic acid.

EXAMPLE 3 Recovery of the Z-keto acid as methyl z -ketod-gluconate without removal of chromium recovered ester has the physical properties listed in Example 2.

adjusting the acidity.

The invention claimed is:

1. Process for preparing 2-keto-aldonic acids which comprises subjecting an aldonate to anodic oxidation in a weakly acid aqueous solution containing a soluble chromium compound and a member selected from the group consisting of alkali metal and alkaline earth metal chlorides and bromides. p

2. Process for preparing Z-keto-aldonic acids which comprises subjecting an aldonate to anodic oxidation in a weakly acid aqueous solution containing chromic acid and a member selected from th group consisting of alkali metal and alkaline earth metal chlorides and bromides.

3. Process for preparing 2-keto-aldonic acids from the soluble alkali or alkaline earth metal salts of the corresponding aldonic acid, which comprises subjecting said salt to anodic oxidation in a weakly acid aqueous solution containing at least one fiftieth of the theoretical amount of a soluble chromium compound calculated as chromium trioxide, and a member selected from the group consisting of the alkali metal and alkaline earth metal chlorides and bromides.

4. Process for preparing 2-keto-aldonic acids from the soluble alkali or alkaline earth metal salts of the corresponding aldonic acid, which comprises subjecting said salt to anodic oxidation in a weakly acid aqueous solution into which has been introduced at least one fiftieth of the theoretical amount of chromium trioxide and a member selected from the group consisting of the alkali metal and alkaline earth metal chlorides and bromides.

5. Process for preparing sodium 2-keto-1-idonate which comprises subjecting sodium-l-idohate to anodic oxidation in a weakly acid aqueous solution into which has been introduced at least one fiftieth of the amount of chromium trioxide theoritically necessary for the oxidation, and sodium bromide.

6. Process for preparing calcium 2-keto-dgluconate which comprises subjecting calcium d-gluconate to anodic oxidation in a'weakly acid aqueous solution into which has been introduced at least one fiftieth of the amount of chromium trioxide theoretically necessary for the oxidation, and calcium bromide.

RICHARD PASTERNACK. PETER P. REGNA.

Certificate of Correction Patent No. 2,222,155. November 19, 1940. RICHARD PASTERNACK ET AL.

It is hereby certified that errors appear in the printed specification of the above numbered patent requiring correction as follows: Page 1, second column, lines27 and 28, for l-idonate read l-idonate; lines 51 and 53 and page 2, second column,

line 58, for keto-1- read kct0-l-; same page 2, second column, line 59, forsodium-1 read sodium-l; and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 7th day of January, A. D. 1941.

[snAL] HENRY VAN ARSDALE,

Acting Commissioner of Patents. 

